Leber Hereditary Optic Neuropathy in a Mother and Daughter Associated With m.10197G>A Mutation.

Abstract

We read with great interest the letter by Jorstad et al (1) describing a 16-year-old boy with Leber hereditary optic neuropathy (LHON) harboring a mitochondrial DNA 10663T>C point mutation and his favorable response to idebenone treatment. We also recently encountered a patient with LHON who had an unusual mitochondrial DNA mutation and experienced marked improvement with idebenone. A 48-year-old woman in excellent health was referred to our neuro-ophthalmology clinic with subacute vision loss in her left eye 2 months previously, followed by right eye involvement 2 weeks later. Her mother had lost vision in a similar manner at a similar age. The patient's visual acuity was 20/50 in the right eye and 20/60 in the left eye. Visual fields demonstrated a central scotoma in each eye, optical coherence tomography showed temporal thinning of the retinal nerve fiber layer bilaterally, and both optic discs were pale temporally. Testing for causes of bilateral optic neuropathy, including MRI of brain and orbits, was unrevealing. Despite a 3-day course of intravenous methylprednisolone (500 mg twice a day), the patient's acuity declined to 20/200 in the right eye and 20/800 in the left eye. Although studies were pending for mitochondrial DNA analysis, the patient was prescribed idebenone (300 mg 3 times a day) and advised to avoid smoking and alcohol. Although testing was negative for the 3 most common LHON mutations, complete mitochondrial DNA sequencing was positive for m.10197G>A mutation, with a heteroplasmy level ranging from 10% to 30%. It was also positive for another mutation (c.116T>G) of unknown clinical significance. Over the next 4 months, the patient's visual acuity improved to 20/25 in the right eye and 20/30 in the left eye. The central scotomas in each eye became less dense. The patient's mother was 70 years old with a history of subacute bilateral visual loss at the age of 58 years. When examined, her acuity was counting fingers in each eye with bilateral cecocentral scotomas and pale optic discs. At the time of her visual loss, her workup included hematologic studies and brain MRI. She, too, did not respond to initial treatment with intravenous corticosteroids. The patient's mother tested negative for the 3 common LHON mutations but declined complete mitochondrial DNA sequencing. The m.10197G>A mutation is a confirmed pathogenic mitochondrial mutation in both the homoplasmic and heteroplasmic forms (2). It changes a hydrophobic alanine residue into a hydrophilic threonine in a highly conserved part of the MT-ND3 of the respiratory chain complex. This mutation has been reported to cause Leigh syndrome and dystonia (3), dystonia and mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes/Leigh syndrome overlap syndrome (4,5). In addition, Wang et al (6) reported 18 patients (9 male; 9 female) with LHON and dystonia in one Chinese family with the m.10197G>A mutation. Ten patients had isolated optic neuropathy without dystonia. Huang et al (7) described a 23-year-old man with isolated LHON who harbored the m.10197G>A mutation. Our patient's presentation was atypical of LHON for a number of reasons: female sex, older age, and the m.10197G>A DNA mutation. Her visual recovery may have occurred spontaneously, although other reports of patients with this mutation have not documented a favorable visual outcome. It seems that idebenone treatment was effective in our patient and in the patient described by Jorstad et al despite having different DNA mutations.